The bombesin-like peptides are widely expressed in mammalian brain, gastro-intestinal tract, normal lung, and cancerous lung. We have made the observation that bombesin-like peptides are also widely expressed in male and female reproductive tract and may play a role in modulating the acrosome reaction, and hence the fertilization of ovum by sperm. Two mammalian bombesin-like peptides have been characterized to date, GRP (gastrin-releasing peptide) and NMB (neuromedin B). Northern blot analysis shows that the GRP receptor is present in spermatocytes. We have shown that treatment of sperm with either GRP or bombesin with doses ranging from 2-100 nanomolar induces the acrosome reaction. The ability of bombesin to stimulate the acrosome reaction can be specifically blocked by GRP receptor antagonists. Preliminary studies have demonstrated that GRP receptor antagonists can also block the efficiency of in vitro fertilization of monkey oocytes. This suggests that GRP receptor antagonists could have contraceptive potential and that, conversely, GRP receptor agonists could enhance the efficiency of in vitro fertilization. Thus, we hypothesize that there is a regulatory pathway in which a bombesin-like peptide is released to modulate the acrosome reaction. One critical question is what is the identity of this bombesin-like peptide. One candidate peptide is the ligand for the bombesin BRS-3 receptor. Using both molecular and conventional isolation techniques, we have been concentrating on isolating the BRS-3 ligand from reproductive tissues.